There is a current need in medicine for innocuous implantable devices that can be delivered to an in vivo patient site, for example, a site in a human patient that can occupy that site for extended periods of time for healing, repair or regeneration of damaged or defective tissue without being harmful to the host. There is currently a further need for such innocuous porous polymeric implantable devices that can eventually become integrated to the damaged or defective tissue site such as to provide biointegrative repair ingrown with tissue or provide bio-integration but which is also at least partially degradable or bioabsorbable to allow for further tissue ingrowth leading to enhanced tissue augmentation and repair at the defect site.
Various tissue engineering (TE) approaches are reviewed in co-pending U.S. Patent Application Publications US 2005/0043816 (now U.S. Pat. No. 7,803,395) and US2007/0190108, U.S. 2010/0318108 and PCT application PCT/US2010/022946 filed Feb. 10, 2010. Tissue engineering generally includes the delivery of a biocompatible tissue substrate that serves as a scaffold or support onto which cells may attach, grow and/or proliferate, thereby synthesizing new tissue by regeneration or new tissue growth to repair a wound or defect. Open cell biocompatible foams with high porosity have been recognized to have significant potential for use in the repair and regeneration of tissue. Tissue engineering has also tended to focus on synthetic bioabsorbable materials because they tend to be absorbed and metabolized by the body without causing significant adverse tissue responses.
Bioabsorbable TE scaffolds have been made using various processing methods and materials such as those described in U.S. Pat. No. 5,522,895 (Mikos), U.S. Pat. No. 5,514,378 (Mikos et al.), U.S. Pat. No. 5,133,755 (Brekke), U.S. Pat. No. 5,716,413 (Walter et al.), U.S. Pat. No. 5,607,474 (Athanasiou et al.), U.S. Pat. No. 6,306,424 (Vyakarnam et. al), U.S. Pat. No. 6,355,699 (Vyakarnam et. al), U.S. Pat. No. 5,677,355 (Shalaby et al.), U.S. Pat. No. 5,770,193 (Vacanti et al.), and U.S. Pat. No. 5,769,899 (Schwartz et al.). Synthetic bioabsorbable biocompatible polymers used in the above-mentioned references are well known in the art and, in most cases, include aliphatic polyesters, homopolymers and copolymers (random, block, segmented and graft) of monomers such as glycolic acid, glycolide, lactic acid, lactide (d-, l-, meso-), ε-caprolactone, trimethylene carbonate, and p-dioxanone or mixtures thereof.
Bioabsorbable polyurethane have been made using various processing methods and materials such as those described in U.S. Pat. No. 7,425,288 (Flodin et al.) and U.S. Pat. No. 6,210,441 (Flodin), U.S. Pat. No. 6,221,997 (Woodhouse, et al), U.S. Pat. No. 6,784,273 (Spaans et. al.), US 2007/0299151 (Guelcher, et al), US 2010/0068171 (Guelcher, et al), US 2009/0221784 (Guelcher, et al), U.S. Pat. No. 7,264,823 (Beckman et al), US 2005/0013793 (Beckman et al), WO 2009/141732 (Van Beijma), WO 2004/074342 (Heijkants, et. al.), US 2010/0068171 (Guelcher, et al), US 2006/0188547 (Bezwada), and US 2009/0292029 (Bezwada).
Various polymers having varying degrees of biodurability or biodegradation are known with the hydrolytic degradation rates being controlled by forming copolymers or blends of various combination of degradable aliphatic polyester homopolymers with different degradation rates. However, some materials are undesirable in view of adverse tissue response during the product's life cycle as the polymers biodegrade. The degradation characteristics of certain materials resist engineering, thus severely limiting their ability to serve as effective scaffolds. Also, there remains a need for an implant that withstands compression in a delivery-device during delivery to a biological site, e.g., by a catheter, endoscope, arthoscope, or syringe, but is capable of expansion by resiliently recovery to occupy and remain in the biological site. Moreover, it has been difficult to engineer controlled pore sizes such that the implant becomes ingrown with tissue, in situ. Furthermore, many materials produced from polyurethane foams formed by blowing during the polymerization process are unattractive from the point of view of biodurability because undesirable materials that can produce adverse biological reactions are generated during polymerization, for example, carcinogens, cytotoxins and the like.